A novel FGD1 mutation in a family with Aarskog-Scott syndrome and predominant features of congenital joint contractures.
A novel FGD1 mutation in a family with Aarskog-Scott syndrome and predominant features of congenital joint contractures.
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DOI：
10.1101/mcs.a000943
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发表时间：
2016-07
影响因子：
1.8
通讯作者：
Keegan CE
中科院分区：
文献类型：
--
作者：
Griffin LB;Farley FA;Antonellis A;Keegan CE
FGD1 突变会导致 Aarskog-Scott 综合征 (AAS)，这是一种 X 连锁疾病，其特征是由于胚胎形态发生和骨骼形成异常而导致面部、骨骼和生殖器发育异常。在这里，我们报告了一个具有非典型 AAS 特征的家族中的一种新的 FGD1 突变，特别是双侧上肢和下肢先天性关节挛缩和心脏异常。男性先证者和他受影响的舅舅对于新的 FGD1 突变 p.Arg921X 是半合子。该变体是 AAS 家族中发现的最羧基末端的 FGD1 突变，预计会在羧基末端 pleckstrin 同源 (PH) 结构域的倒数第二个氨基酸处截断 FGD1 蛋白。我们的研究强调了 3' 肽序列在 FGD1 蛋白结构和/或功能中的重要性，并进一步证明需要筛查 X 连锁先天性关节挛缩患者的 FGD1 突变。
Mutations in FGD1 cause Aarskog–Scott syndrome (AAS), an X-linked condition characterized by abnormal facial, skeletal, and genital development due to abnormal embryonic morphogenesis and skeletal formation. Here we report a novel FGD1 mutation in a family with atypical features of AAS, specifically bilateral upper and lower limb congenital joint contractures and cardiac abnormalities. The male proband and his affected maternal uncle are hemizygous for the novel FGD1 mutation p.Arg921X. This variant is the most carboxy-terminal FGD1 mutation identified in a family with AAS and is predicted to truncate the FGD1 protein at the second to last amino acid of the carboxy-terminal pleckstrin homology (PH) domain. Our study emphasizes the importance of the 3′ peptide sequence in the structure and/or function of the FGD1 protein and further demonstrates the need to screen patients with X-linked congenital joint contractures for FGD1 mutations.